Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Trial Contact Information
Related Information
Registry Information

Alternate Title

Vaccine Therapy With or Without Sargramostim in Treating Patients With Metastatic Prostate Cancer

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II, Phase I Treatment Closed 18 and over NCI NCI-03-C-0176 03-C-0176, NCI-5911, 5911, NCT00062153

Objectives

1. Determine the safety and toxicity of sequential vaccination with vaccinia-PSA-TRICOM vaccine and fowlpox-PSA-TRICOM vaccine in patients with metastatic prostate cancer. (Phase I closed to accrual as of 6/2/04.)
2. Determine the impact of sargramostim (GM-CSF) and fowlpox-GM-CSF on immunologic response in patients treated with these vaccines.
3. Determine the change in prostate-specific antigen-specific T cells in patients treated with these vaccines.
4. Determine objective antitumor response in patients treated with these vaccines.

Entry Criteria

Disease Characteristics:

• Histologically confirmed prostate cancer, meeting the following criteria:
  • Metastatic disease
  • Androgen insensitive



• Progression after prior standard hormonal therapy for metastatic prostate cancer
  • Prior antiandrogen therapy requires a rising prostate-specific antigen (PSA) after withdrawal of at least 4 weeks
  • Prior bicalutamide therapy requires a rising PSA after withdrawal of at least 6 weeks



• Objective evidence of metastasis or relapsing local disease as evidenced by a rising PSA and at least 1 of the following:
  • Positive bone scan
  • Palpable disease
  • The following positive imaging studies:
    • Two consecutively rising PSA levels taken at least 1 week apart, with 1 level that is 50% above the nadir reached after the last therapeutic maneuver (as long as the last measurement is at least 5 ng/mL)
    • At least 1 lesion consistent with metastatic cancer on technetium Tc 99m whole body scintigraphy

      AND/OR

    • Soft-tissue metastases as measured by appropriate modalities (i.e., imaging and palpation)



• HLA-A2 positive (phase II only)



• No brain metastases

Prior/Concurrent Therapy:

Biologic therapy

• No prior PSA vaccine therapy (phase II only)

Chemotherapy

• More than 3 years since prior therapy with any of the following (phase II only):
  • Docetaxel
  • Paclitaxel
  • Doxorubicin
  • Cisplatin
  • Carboplatin
  • Mitoxantrone
  • Estramustine
  • Cyclophosphamide
  • Irinotecan
  • Topotecan

Endocrine therapy

• See Disease Characteristics
• No concurrent steroid therapy (except topical or inhaled steroids)
• Patients concurrently receiving luteinizing hormone-releasing factor analog therapy must continue therapy during study participation

Radiotherapy

• At least 4 weeks since prior radiotherapy

Surgery

• No prior splenectomy

Other

• Recovered from all prior therapy
• No concurrent antibiotics
• No other concurrent antitumor therapy

Patient Characteristics:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• More than 6 months

Hematopoietic

• Granulocyte count at least 1,500/mm³
• Platelet count at least 100,000/mm³
• Lymphocyte count at least 500/mm³
• Hemoglobin at least 10 g/dL

Hepatic

• Bilirubin less than 1.5 mg/dL
• AST and ALT less than 2.5 times upper limit of normal
• Hepatitis B negative
• Hepatitis C negative

Renal

• Creatinine clearance greater than 60 mL/min
• Creatinine normal
• No proteinuria 1,000 mg or greater by 24-hour urine collection
• No hematuria*
• No abnormal sediment*

 [Note: *Patient may be eligible provided the underlying cause is determined to be non-renal]

Cardiovascular

• No prior unstable or newly diagnosed angina pectoris
• No myocardial infarction within the past 6 months
• No New York Heart Association class II-IV congestive heart failure
• No clinically significant cardiomyopathy requiring treatment

Immunologic

• HIV negative
• No active infection within the past 3 days
• No allergy or untoward reaction to prior vaccinia virus vaccination
• No concurrent significant autoimmune disease that is active or potentially life-threatening if activated
• No known allergy to eggs

Other

• Fertile patients must use effective contraception
• No other active malignancy within the past 2 years except nonmelanoma skin cancer or carcinoma in situ of the bladder
• No other concurrent serious or life-threatening illness
• No eczema or eczematoid skin disorders
• No acute, chronic, or exfoliative skin conditions, including:
  • Atopic dermatitis
  • Burns
  • Impetigo
  • Varicella zoster
  • Severe acne
  • Other open rashes or wounds
• No close household contact with persons meeting any of the following criteria for at least 3 weeks after vaccination:
  • Prior or active eczema or other eczematoid skin disorders
  • Acute, chronic, or exfoliative skin conditions (e.g., atopic dermatitis, burns, impetigo, varicella zoster, severe acne, or other open rashes or wounds)
  • Pregnant or nursing women
  • Children under 5 years of age
  • Immunodeficient or immunosuppressed (including HIV infection) individuals
• Willing and able to travel to the National Institutes of Health for follow-up

Expected Enrollment

A maximum of 62 patients (up to 30 for phase I [closed to accrual as of 6/2/04] and a total of 32 [8 per treatment arm] for phase II) will be accrued for this study within 2 years.

Outcomes

T cell precursor frequency as measured by Enzyme-linked ImmunoSpot Assay (ELISPOT) assay

Clinical response

Outline

This is a pilot phase I dose-escalation study (phase I closed to accrual as of 6/2/04) followed by a randomized phase II study.

• Phase I (closed to accrual as of 6/2/04): Cohorts of 3-6 patients are sequentially assigned to 1 of 5 treatment regimens to determine the optimal regimen. The optimal regimen is defined as the regimen preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
  • Regimen A: Patients receive fowlpox-PSA-TRICOM vaccine (F-PSA-TRI) subcutaneously (SC) on days 1, 29, and 57.
  
  
  
  • Regimen B: Patients receive vaccinia-PSA-TRICOM vaccine (VPSA-TRI) SC on day 1 and F-PSA-TRI SC on days 29 and 57.
  
  
  
  • Regimen C: Patients receive VPSA-TRI and F-PSA-TRI as in regimen B and sargramostim (GM-CSF) SC on days 1-4, 29-32, and 57-60.
  
  
  
  • Regimen D: Patients receive VPSA-TRI and F-PSA-TRI as in regimen B and fowlpox-sargramostim (rf-GM-CSF) SC on days 1, 29, and 57.
  
  
  
  • Regimen E: Patients receive VPSA-TRI and F-PSA-TRI as in regimen B and a higher dose of rf-GM-CSF as in regimen D.
  
  
  



• Phase II: Patients are randomized to 1 of 4 treatment arms, based on the assumption that all 5 regimen levels in phase I are completed.
  • Arm I: Patients receive VPSA-TRI and F-PSA-TRI as in regimen B.
  
  
  
  • Arm II: Patients receive VPSA-TRI, F-PSA-TRI, and GM-CSF as in regimen C.
  
  
  
  • Arm III: Patients receive VPSA-TRI, F-PSA-TRI, and rf-GM-CSF as in regimen D.
  
  
  
  • Arm IV: Patients receive VPSA-TRI, F-PSA-TRI, and rf-GM-CSF as in regimen E.
  
  
  

Patients in both phases who do not have disease progression after day 85 may receive monthly F-PSA-TRI vaccinations for 12 weeks, according to their assigned treatment arm. Patients are re-evaluated on day 170 and receive an additional F-PSA-TRI vaccination with subsequent F-PSA-TRI vaccinations every 12 weeks thereafter in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed annually for 15 years.

Arlen PM, Gulley J, Dahut W, et al.: A phase I study of sequential vaccinations with recombinant Fowlpox-PSA (L155)-TRICOM (rF) alone, or in combination with recombinant vaccinia-PSA (L155)-TRICOM (rV), and the role of GM-CSF, in patients (Pts) with prostate cancer. [Abstract] J Clin Oncol 22 (Suppl 14): A-2522, 168s, 2004.

Trial Contact Information

Trial Lead Organizations

NCI - Center for Cancer Research

James Gulley, MD, PhD, Principal investigator		Ph: 301-435-2956 Email: gulleyj@mail.nih.gov

Related Information

Featured trial article

Registry Information
Official Title		A Phase I/II Pilot Study Of Sequential Vaccinations With rFowlpox-PSA (L155)-Tricom (PROSTVAC-F/TRICOM) Alone, Or In Combination With rVaccinia-PSA(L155)-TRICOM (PROSTVAC-V/TRICOM), And The Role Of GM-CSF, In Men With Prostate Cancer
Trial Start Date		2003-05-12
Trial Completion Date		2006-02-28 (estimated)
Registered in ClinicalTrials.gov		NCT00062153
Date Submitted to PDQ		2003-04-28
Information Last Verified		2007-01-10

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